. This proposal describes the chemical development of a novel pulsed transdermal therapeutic system (TTS) using existing and conceptualized Intelimer TM polymeric membranes proprietary to Landec Labs. Ultimately, the system will enable pulsed, ramp, and diurnal dosing regimens. Potential benefits derived from such a system include the reduction of tolerance, improved patient compliance, and patient controlled therapy. The heart of the pulsed transdermal system is the Intelimer TM class of polymeric controlled release materials. These polymers have a very low permeability to a variety of drugs below a "switch temperature' and a very high permeability above that temperature. The work to be performed in this research proposal will focus on optimizing these polymers and the membranes prepared from them. The flux of selected model drug compounds through the membranes will be measured as a function of temperature.Diffusion parameters will be computed and these results will be used to modify and optimize the polymer materials to achieve the desired "switch temperature" and release rate. Finally, laminating techniques will be established and in vitro release profiles of the laminated device will be measured.